dc.contributor.author | Woolston, A | |
dc.contributor.author | Khan, K | |
dc.contributor.author | Spain, G | |
dc.contributor.author | Barber, LJ | |
dc.contributor.author | Griffiths, B | |
dc.contributor.author | Gonzalez-Exposito, R | |
dc.contributor.author | Hornsteiner, L | |
dc.contributor.author | Punta, M | |
dc.contributor.author | Patil, Y | |
dc.contributor.author | Newey, A | |
dc.contributor.author | Mansukhani, S | |
dc.contributor.author | Davies, MN | |
dc.contributor.author | Furness, A | |
dc.contributor.author | Sclafani, F | |
dc.contributor.author | Peckitt, C | |
dc.contributor.author | Jiménez, M | |
dc.contributor.author | Kouvelakis, K | |
dc.contributor.author | Ranftl, R | |
dc.contributor.author | Begum, R | |
dc.contributor.author | Rana, I | |
dc.contributor.author | Thomas, J | |
dc.contributor.author | Bryant, A | |
dc.contributor.author | Quezada, S | |
dc.contributor.author | Wotherspoon, A | |
dc.contributor.author | Khan, N | |
dc.contributor.author | Fotiadis, N | |
dc.contributor.author | Marafioti, T | |
dc.contributor.author | Powles, T | |
dc.contributor.author | Lise, S | |
dc.contributor.author | Calvo, F | |
dc.contributor.author | Guettler, S | |
dc.contributor.author | von Loga, K | |
dc.contributor.author | Rao, S | |
dc.contributor.author | Watkins, D | |
dc.contributor.author | Starling, N | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Sadanandam, A | |
dc.contributor.author | Cunningham, D | |
dc.contributor.author | Gerlinger, M | |
dc.date.accessioned | 2019-06-27T09:06:48Z | |
dc.date.issued | 2019-06-26 | |
dc.identifier.citation | Cancer cell, 2019, 36 (1), pp. 35 - 50.e9 | |
dc.identifier.issn | 1535-6108 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3276 | |
dc.identifier.eissn | 1878-3686 | |
dc.identifier.doi | 10.1016/j.ccell.2019.05.013 | |
dc.description.abstract | Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS wild-type CRCs identified associations of NF1 and non-canonical RAS/RAF aberrations with primary resistance and validated transcriptomic CRC subtypes as non-genetic predictors of benefit. Sixty-four percent of biopsies with acquired resistance harbored no genetic resistance drivers. Most of these had switched from a cetuximab-sensitive transcriptomic subtype at baseline to a fibroblast- and growth factor-rich subtype at progression. Fibroblast-supernatant conferred cetuximab resistance in vitro, confirming a major role for non-genetic resistance through stromal remodeling. Cetuximab treatment increased cytotoxic immune infiltrates and PD-L1 and LAG3 immune checkpoint expression, potentially providing opportunities to treat cetuximab-resistant CRCs with immunotherapy. | |
dc.format | Print | |
dc.format.extent | 35 - 50.e9 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Biopsy | |
dc.subject | Prognosis | |
dc.subject | Treatment Outcome | |
dc.subject | Gene Expression Profiling | |
dc.subject | DNA Mutational Analysis | |
dc.subject | Computational Biology | |
dc.subject | Immunity | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Mutation | |
dc.subject | Kaplan-Meier Estimate | |
dc.subject | Molecular Targeted Therapy | |
dc.subject | Transcriptome | |
dc.subject | ErbB Receptors | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Antineoplastic Agents, Immunological | |
dc.title | Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-05-23 | |
rioxxterms.versionofrecord | 10.1016/j.ccell.2019.05.013 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancer cell | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Oncogenomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structural Biology of Cell Signalling | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Oncogenomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structural Biology of Cell Signalling | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.publication-status | Published | |
pubs.volume | 36 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Gastrointestinal Cancers Clinical Trials | |
icr.researchteam | Medicine (RMH Smith Cunningham) | |
icr.researchteam | Systems and Precision Cancer Medicine | |
icr.researchteam | Translational Oncogenomics | |
icr.researchteam | Structural Biology of Cell Signalling | |
dc.contributor.icrauthor | Woolston, Andrew | |
dc.contributor.icrauthor | Spain, Georgia | |
dc.contributor.icrauthor | Punta, Marco | |
dc.contributor.icrauthor | Newey, Alice | |
dc.contributor.icrauthor | Furness, Andrew | |
dc.contributor.icrauthor | Lise, Stefano | |
dc.contributor.icrauthor | Guettler, Sebastian | |
dc.contributor.icrauthor | Gerlinger, Marco | |